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学科主题: 临床医学
题名:
Humanization of a mouse monoclonal antibody neutralizing TNF-alpha by guided selection
作者: Wang, ZZ1; Wang, Y1; Li, ZF1; Li, J1; Dong, ZW1
关键词: tumor necrosis factor alpha ; phage display ; recombinant antibody libraries ; human antibody
刊名: JOURNAL OF IMMUNOLOGICAL METHODS
发表日期: 2000-07-31
卷: 241, 期:1-2, 页:171-184
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biochemical Research Methods ; Immunology
研究领域[WOS]: Biochemistry & Molecular Biology ; Immunology
关键词[WOS]: TUMOR-NECROSIS-FACTOR ; HYPERVARIABLE REGIONS ; RHEUMATOID-ARTHRITIS ; FAB FRAGMENTS ; V(H) SEGMENTS ; SEPTIC SHOCK ; REPERTOIRE ; LIBRARIES ; AFFINITY ; REVEALS
英文摘要:

With the advent of phage display antibody libraries, humanization of murine antibodies can be achieved by epitope guided selection. In present study, guided selection was applied to the humanization of the mouse mAb Z8 that is directed to human TNF-alpha and can neutralize the cytotoxicity of TNF-alpha. First, the Z8 Fd gene was paired as a template with a repertoire of human kappa chains, and displayed on the filamentous phage, forming a hybrid phage antibody library. Selected by four rounds of panning against TNF-alpha, hybrid antibody fragments that bound to TNF-alpha and contained human kappa chains were obtained. Meanwhile human Fd genes were selected by pairing the human Fd repertoire with the Z8 kappa chain and performing the same procedure of panning. One of the isolated human Fd genes (huFd2), which showed the strongest reactivity, was chosen to pair with 12 of selected human kappa chains. Two of the resulting human Fabs (huFd2-hu kappa 1 and huFd2-hu kappa 2), with same Fd and different kappa chains, bound to TNF-alpha specifically. Their human origin was proved by ELISA and sequencing analysis. The human Fabs competitive ELISA and in vitro TNF-alpha neutralization assay demonstrated that the human Fabs resembled its parental mouse mAb Z8 in that they both recognized the same epitope and neutralized the cytotoxicity of TNF-alpha. These results suggest that guided selection is a promising strategy in murine mAb humanization. (C) 2000 Elsevier Science BN. All rights reserved.

语种: 英语
WOS记录号: WOS:000088641200016
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/51520
Appears in Collections:北京大学临床肿瘤学院_期刊论文

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作者单位: 1.Navy Gen Hosp, Cent Lab, Beijing 100037, Peoples R China
2.Beijing Med Univ, Beijing Inst Canc Res, Beijing 100034, Peoples R China
3.Canc Hosp, Chinese Acad Med Sci, Beijing 100020, Peoples R China

Recommended Citation:
Wang, ZZ,Wang, Y,Li, ZF,et al. Humanization of a mouse monoclonal antibody neutralizing TNF-alpha by guided selection[J]. JOURNAL OF IMMUNOLOGICAL METHODS,2000,241(1-2):171-184.
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